MicroRNA-422a functions as a tumor suppressor in non-small cell lung cancer through SULF2-mediated TGF-ß/SMAD signaling pathway.

Li, Wei-Qiang; Zhang, Jian-Peng; Wang, Yan-Yu; Li, Xin-Zhen; Sun, Lin

Li, Wei-Qiang; Zhang, Jian-Peng; Wang, Yan-Yu; Li, Xin-Zhen; Sun, Lin.

Afiliación

Li WQ; a Department of Thoracic Surgery , Beijing Luhe Hospital, Capital Medical University , Beijing , P. R. China.
Zhang JP; a Department of Thoracic Surgery , Beijing Luhe Hospital, Capital Medical University , Beijing , P. R. China.
Wang YY; a Department of Thoracic Surgery , Beijing Luhe Hospital, Capital Medical University , Beijing , P. R. China.
Li XZ; a Department of Thoracic Surgery , Beijing Luhe Hospital, Capital Medical University , Beijing , P. R. China.
Sun L; a Department of Thoracic Surgery , Beijing Luhe Hospital, Capital Medical University , Beijing , P. R. China.

Cell Cycle ; 18(15): 1727-1744, 2019 08.

Article en En | MEDLINE | ID: mdl-31204561

RESUMEN

MicroRNAs (miRNAs) have been demonstrated to participate in a variety of human cancers by functioning as post-transcriptional regulators of oncogenes or antioncogenes including non-small cell lung cancer (NSCLC). The aim of the current study was to identify the role of miR-422a in NSCLC via sulfatase 2 (SULF2) to further elucidate the mechanism of NSCLC. Initially, the expression of miR-422a and SULF2 was determined in NSCLC tissues and cells. The role of miR-422a in NSCLC was identified in relation with a miR-422a mimic or inhibitor, siRNA against SULF2 and TGF-ß1. The regulatory effects of miR-422a were examined following detection of the related epithelial mesenchymal transition (EMT)-related genes, and the apoptosis-related genes and evaluation of their cellular biological functions. The expression pattern of miR-422a, SULF2, and the TGF-ß/SMAD pathway-related genes was detected to elucidate the mechanism by which miR-422a influences the progression of NSCLC. Finally, xenograft tumors in nude mice were observed for tumorigenicity evaluation purposes. Our results showed that miR-422a was poorly expressed while SULF2 was highly expressed in NSCLC. Dual luciferase reporter gene assay further verified that miR-422a targeted SULF2. Altogether, this study demonstrated that miR-422a downregulated SULF2 to inhibit the TGF-ß/SMAD pathway. NSCLC cell proliferation, migration, invasion, colony formation, EMT and tumorigenesis were all inhibited while apoptosis was promoted upon restoration of miR-422a or silencing of SULF2. However, the activation of the TGF-ß/SMAD pathway was determined to reverse the tumor-suppressive effects of si-SULF2. miR-422a restoration, which ultimately inhibited the progression of NSCLC by suppressing the TGF-ß/SMAD pathway via SULF2.

Asunto(s)

Carcinoma de Pulmón de Células no Pequeñas/metabolismo; Neoplasias Pulmonares/metabolismo; MicroARNs/metabolismo; Proteínas Smad/metabolismo; Sulfatasas/metabolismo; Factor de Crecimiento Transformador beta1/metabolismo; Animales; Apoptosis/efectos de los fármacos; Apoptosis/genética; Carcinogénesis/genética; Carcinoma de Pulmón de Células no Pequeñas/enzimología; Carcinoma de Pulmón de Células no Pequeñas/genética; Carcinoma de Pulmón de Células no Pequeñas/patología; Línea Celular Tumoral; Movimiento Celular/efectos de los fármacos; Movimiento Celular/genética; Proliferación Celular/efectos de los fármacos; Proliferación Celular/genética; Biología Computacional; Transición Epitelial-Mesenquimal/efectos de los fármacos; Transición Epitelial-Mesenquimal/genética; Femenino; Regulación Neoplásica de la Expresión Génica/efectos de los fármacos; Regulación Neoplásica de la Expresión Génica/genética; Silenciador del Gen; Genes Supresores de Tumor; Humanos; Neoplasias Pulmonares/enzimología; Neoplasias Pulmonares/genética; Neoplasias Pulmonares/patología; Ratones; Ratones Desnudos; MicroARNs/genética; ARN Interferente Pequeño; Transducción de Señal/genética; Proteínas Smad/genética; Sulfatasas/genética; Factor de Crecimiento Transformador beta1/farmacología; Trasplante Heterólogo

Palabras clave

Sulfatase 2; TGF-ß/SMAD signaling pathway; colony formation; epithelial mesenchymal transition; microRNA-422a; non-small cell lung cancer

Texto completo

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sulfatasas / Carcinoma de Pulmón de Células no Pequeñas / MicroARNs / Proteínas Smad / Factor de Crecimiento Transformador beta1 / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Idioma: En Revista: Cell Cycle Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Buscar en Google